tbuckley/cabot-search huggingface dataset:
Real world outcome of neuroendocrine carcinomas of the bladder compared to conventional tumors of the bladder.
Authors: Serhan Unlu, Olisaemeka Ogbue, Abdel Rahman Nanah, Sharmeen Sorathia, Nima Almassi, James Lapinski, Abdo S. Haddad, Hamed Daw
Journal: Journal of Clinical Oncology (2023)

e16591 Background: Platinum based neoadjuvant chemotherapy (NAC) has been shown to be a beneficial treatment strategy that increases overall survival (OS) in bladder cancer (BC) when compared to radical cystectomy (RC) alone, and the benefit was observed in multiple histologies associated with BC. Neuroendocrine carcinomas (NEC) of the bladder are a rare and aggressive BC subtype known to be chemotherapy sensitive, with improvement in oncological outcomes after NAC. However, due to inherent differences in natural progression of different BC histologies, higher chemosensitivity does not necessarily mean NEC has better outcomes compared to other BC histologies after NAC. We analyzed the outcomes of NEC patients and non-NEC BC patients to investigate the differences in benefit observed from NAC, and in oncological outcomes. Methods: Patients with BC that underwent cystectomy from 2000 to 2022 at the Cleveland Clinic Foundation were identified. Patients with NEC at transurethral resection (TUR) or cystectomy, and patients with BC with other pathologies (non-NEC) were selected. pCR was defined as downstaging from tumor presence in diagnostic resection to no residual tumor (pT0N0) after NAC. Survival outcomes of interest included recurrence-free survival (RFS) and OS. Results: A total of 562 cases of BC that underwent RC were identified. Of these, 50 patients included a diagnosis of NEC in their pathology report, either in TUR (n=42), or in RC (n=8) with 36% (18/50) of them with NEC without an associated conventional urothelial cell carcinoma (UCC), while 502 patients were diagnosed with UCC, with or without variant histologies and 10 patients with other histologies without UCC. Among patients with NEC, median age was 69 and M:F-45:5. When NEC patients were compared to non-NEC BC patients, they were more likely to present with muscle invasive bladder cancer (MIBC), (83% vs 60%; p=0.003) and receive NAC (86% vs 35%; p&lt;0.001) Most common chemotherapy regimen used in NEC patients was combination platinum and etoposide (26/36), compared to platinum and gemcitabine in non-NEC BC patients (141/184). pCR rate was 36% (13/36) in NEC, compared to 20% (36/184) in non-NEC cohort. (p=0.046). In terms of survival outcomes, RFS and OS were similar between the two groups (log-rank p-values 0.08 and 0.14, respectively). Conclusions: NAC prior to RC is beneficial in NEC of the bladder as a higher proportion achieve pCR when compared to non-NEC BC. In our cohort, despite presenting with more advanced disease, oncologic outcomes after NAC with RC were similar between the two groups. [Table: see text]
Upgrading the non-gene-editing, allogeneic ThisCART platform for extending persistence in vivo.
Authors: Kaichun Liu, Z Pc, Ling He, Yinhang Zhang, Shanshan Chen, Yuchen Jiang, Guanggui Xu, Jianmin Fu, Baolei Wang, Sujun Li, Xingbing Wang, Jun Li
Journal: Journal of Clinical Oncology (2023)

e14569 Background: Lack of in vivo persistence is the major challenge in allogeneic CAR-T field. Various HLA-related gene-editing strategies are being explored to prevent rejection by host T and NK cells (Table 1). This study reports a platform upgrade on ThisCART (TCR and HLA-I intracellular sequestered), represented by ThisCART19C cells. Methods: ThisCART19C cells were produced with a single lentivirus vector, encoding a CD19-targeting CAR, a KDEL-tagged anti-CD3 scFv, and the HCMV US11 protein. The surface expression of CAR19, TCRαβ and HLA-A/B/E was measured by flow cytometer. Specific tumor cytotoxicity was evaluated both in vitro and in vivo. Furthermore, the safety of donor derived ThisCART19C cells were tested in a xenogeneic GvHD model. Results: Similar to our ThisCART19A product currently in multi-center trials, ThisCART19C cells were readily produced to a quantity and quality supporting clinical investigation. ThisCART19C cells demonstrated an anticipated and stable surface immunotype: CAR19 + , TCRαβ - , HLA-A - , HLA-B - ，HLA-E + ，with great potential for simultaneous evasion of both host T and NK cells. Similar to autologous CD19-directed CAR-T, ThisCART19C exhibited potent CD19-specific cytotoxicity in vitro and in vivo. No xenogeneic GvHD reaction was observed in murine model over an extended period. Conclusions: To our knowledge, ThisCART19C represents the first application of viral evading strategy in promoting the clinical persistence of allogeneic CAR-T cells. Its efficient processing, potent cytotoxicity and favored preclinical safety profile warrant clinical investigation. [Table: see text]
Preliminary results of sequential transarterial chemoembolization and stereotactic body radiotherapy followed by immunotherapy using single tremelimumab regular interval durvalumab in locally advanced, unresectable hepatocellular carcinoma (START-FIT using STRIDE): A single-arm, phase II study.
Authors: Chi Leung Chiang, Stephen Lam Chang, Sik-Kwan Chan, Ann Shing Lee, Keith Wan Hang Chiu, Vanessa Ting Yan Yeung, Natalie Sean Man Wong, Venus Wan Yan Lee, Vince Wing Hang Lau, Nancy Kwan Man, Feng-Ming Spring Kong, Albert Chi Yan Chan
Journal: Journal of Clinical Oncology (2023)

4124 Background: Sequential transarterial chemoembolization and stereotactic body radiotherapy followed by immunotherapy (IO) (START-FIT) using anti-PD-L1 has demonstrated promising efficacy in locally advanced HCC (laHCC). We aimed to evaluate START-FIT activity using anti-PD-L1 and anti-CTLA-4 IO backbone. Methods: Adult patients with laHCC not suitable for curative resections were recruited. Each with tumor at least 5cm, maximum three tumors, and child-Pugh A5-B7 liver function. Patients had single TACE, 5-SBRT 28 days after, then single Tremelimumab (300mg) and regular 4-week interval Durvalumab (1500mg) at 7 days upon SBRT completion. Primary endpoint was overall response rate (ORR) per modified Response Evaluation Criteria in Solid Tumors (mRECIST); secondary endpoints included progression-free survival (PFS), overall survival (OS), and treatment-related (TR) adverse event (AE) [NCT04988945]. Results: During 11 Dec, 20 and 3 Oct, 22, 16 patients were enrolled with median age 66 (range (r): 51–84 years), 14 (87.5%) were male, the lesion(s) diameter median sum was 11.2 cm (r: 5.8–15cm), and 11 (68.8%) had macrovascular invasion (n=6, hepatic vein, n=4, branched portal vein, n=1 both). With median 11.3 months (r: 3.7–24.5 months) follow-up time, the best ORR was 81.3% (95% CI: 54.4–96.0%) (Complete response CR: n=7, 43.8%; partial response PR: n=6, 37.5%; static disease SD + progressive disease PD: n=3, 18.7%). The 6 and 12-month PFS rates was 86.7% (95% CI: 69.3–100%) and 58.7% (95% CI: 33.6–84.4%), while 6 and 12-month OS rates was 100% (95% CI: 91.7–100%) and 83.3% (95% CI: 62.2–100%) respectively. The 12-month OS with CR vs. PR vs. SD+PD was 100%, 75%, and 50% respectively. Four (25%) and one patient (6.3%) experienced TRAEs and immune-related AE of grade 3 or worse respectively. Conclusions: START-FIT using STRIDE is safe and effective in unresectable laHCC resulted in 43.8% CR rate and promising survival. Clinical trial information: NCT04988945 . [Table: see text]
Anlotinib hydrochloride combined with tislelizumab, paclitaxel liposome, and nedaplatin regimen for preoperative neoadjuvant therapy of esophageal cancer: A single-arm, single-center, phase II exploratory clinical study.
Authors: Jie Ma, Cuizhen Liu, Shi-xue Laoguo, Huafu Zhou, Yongyong Wang, Jianji Guo, Lihua Yang, Jing Tang, Rong Li, Zhiming Zeng, Lei Dai, Ning Mo, Jie Zeng
Journal: Journal of Clinical Oncology (2023)

e16082 Background: Local recurrence and distant metastasis are important causes of high mortality in patients with locally advanced esophageal cancer. Neoadjuvant therapy combined with surgery can significantly improve the prognosis of patients with locally advanced esophageal cancer. Based on the clinical data of anlotinib (a multi-targeted tyrosine kinase inhibitors) and tislelizumab (anti-pd-1 antibodies), paclitaxel liposome (a cytotoxic anti-tumor drugs) and nedaplatin (a platinum-based anti-tumor drugs) in patients with esophageal cancer, to evaluate the efficacy and safety of anlotinib hydrochloride combined with tislelizumab, paclitaxel liposome and nedaplatin in preoperative neoadjuvant therapy for patients with stage IIB-IVA esophageal cancer. Methods: This study included 18-75 years old, ECOG PS 0-1 patients with potentially resectable stage IIB-IVA esophageal cancer with a predicted survival time of ≥12 weeks and confirmed by histopathology or cytology. Patients who met the inclusion criteria received anlotinib (oral, 12mg/d1-14,Q3W) combined with tislelizumab (intravenous drip, 200mg/d1,Q3W), paclitaxel liposome (intravenous drip, 175mg/m2/d1,Q3W) and nedaplatin (intravenous drip, 80mg/m2/d1,Q3W). After 2 cycles of neoadjuvant therapy, surgery was performed, and 4-6 weeks of chemotherapy combined with targeted immune adjuvant therapy was performed after the operation, and then Anlotinib combined with tislelizumab targeted immune maintenance therapy was performed until the disease progressed. Subjects who failed to complete at least one cycle of clinical trials according to this program due to non-experimental drug factors, and seriously violated this research program, such as: failure to follow the prescribed dose, method and course of medication, will be excluded from this study. The primary endpoint was objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), R0 resection rate, and pathological complete response rate. Results: From October 2021 to February 2023, 38 patients were included in this study, and clinical data of 27 patients can be used to track and evaluate clinical efficacy. The median age of the subjects was 58.5 years (range 47-75 years). the primary study end point was an ORR of 77.8% (95% CI，61%-94.5%). Conclusions: We will strictly implement the research protocol and objectively evaluate the anti-tumor activity and safety of anlotinib hydrochloride combined with tislelizumab, paclitaxel liposome and nedaplatin regimen in the treatment of patients with stage IIB ~ IVA esophageal cancer. In order to provide a safe and reliable neoadjuvant therapy for patients with locally advanced esophageal cancer. Clinical trial information: ChiCTR2100049693 .
Radiotherapy alone versus concurrent or adjuvant chemoradiotherapy for nasopharyngeal carcinoma patients with negative Epstein-Barr virus DNA post-induction chemotherapy.
Authors: Fang-Fang Kong, Guang-Sen Pan, Cheng-Run Du, Zhen Zhang, Chaosu Hu, Hong-Mei Ying
Journal: Journal of Clinical Oncology (2023)

6064 Background: Induction chemotherapy (IC) plus concurrent chemoradiotherapy has been recommended as the standard treatment for locoregionally advanced nasopharyngeal carcinoma(LA-NPC). However, concurrent chemotherapy was associated with increased toxicities, poor tolerance, and low completion rates. The aim of this study was to compare the efficacy and toxicity of IC+ radiotherapy (RT) and IC+ concurrent or adjuvant chemoradiotherapy (IC+CCRT/AC) in patients with negative post-IC EBV DNA. Methods: A total of 547 NPC patients with negative plasma EBV DNA post-IC were included. Patients were classified into the IC+RT group and the IC+ concurrent or adjuvant chemoradiotherapy (IC+CCRT/AC) group. Locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS) were estimated and compared using the Kaplan-Meier method. Propensity-score matching (PSM) was performed to balance the variables. Results: The median follow-up time was 37 months. The 3-year LRFS, DMFS, OS, and PFS rates for the whole group were 92.2%, 92.4%, 96.4%, and 84.4%, respectively. There was no significant difference in LRFS, DMFS, OS, and PFS between the IC+RT and the IC+CCRT/AC group both before PSM (3-year rates of 91.1% vs. 92.6%, p = 0.94; 95.6% vs. 91.5%, p = 0.08; 95.2% vs. 96.8%, p = 0.80; 85.9% vs. 84.0%, p = 0.38) and after PSM (90.7% vs. 92.7%, p = 0.77; 96.8% vs. 93.7%, p = 0.29; 94.5% vs. 93.9%, p = 0.57; 84.7% vs. 85.6%, p = 0.96). Multivariate analysis demonstrated that treatment schedule was not an independent predictor for survival rates. Patients in the IC+RT group had fewer treatment-related acute toxicities and better tolerance. Conclusions: IC+RT displayed similar survival outcomes as IC+CCRT/AC for NPC patients with negative post-IC EBV DNA. Our current data seems not to support the routine use of concurrent or adjuvant chemotherapy after IC for unselected patients.
Lack of organization to access cancer treatment in southeast Brazil: Urgent need to change.
Authors: Sabina B. Aleixo, Jose Zago Pulido, Narelle Parmanhane, Darcy Fassarela, Ana Paula Fonseca
Journal: Journal of Clinical Oncology (2023)

e18516 Background: Healthcare access is a fundamental component in achieving universal health coverage, the central commitment of the Brazilian Unified Health System (SUS). In Brazil, primary healthcare centers from the cities refer suspected or confirmed cases of cancer to accredited oncology services in their regions. Methods: This is a qualitative exploratory study aiming to knowing the functioning of the cancer care network in 26 cities of the Southern Region of the State of Espírito Santo/Brazil (686,450 inhabitants) that refer patients to an SUS-accredited oncology center.The information was collected during the year 2022 through semi-structured interviews with cities health departments. Results: Regarding the extent of the Primary Health Care Service (PHCS), the results showed that only 14 cities (54%) have 100% of their territory covered, while the others have coverage ranging from 75% to 98%. With regard to medical work in PHCS units, it was found adequate in 17 (65% )cities and not adequate in the other 9 (35% ); however, their was only 2 licensed physicians in Family Medicine working the cities. The number of patients being treated is known in just 5 (19%) cities and as far as transport to the treatment center, 16 (62%) cities report that meet the demand and 10 (32%) that do not. Finally, no city had a support service to help patients navigate the public health system. Conclusions: The results indicate that Access to basic health services is insufficient in the Southern region of the State of Espirito Santo, and that the organization of the cancer care network needs to be improved with more resources and trained medical professionals.
Pre-clinical efficacy of the first glyco-humanized oncolytic polyclonal antibody (XON7) in onco-hematology.
Authors: Carine Ciron, Françoise Shneiker, Odile Duvaux
Journal: Journal of Clinical Oncology (2023)

e14519 Background: Polyclonal antibodies pAb were shown to possess oncolytic properties a century ago with reported clinical responses. More recent pre-clinical models confirmed pAb efficacy though their ability to tackle complex target antigens. The emergence of escape variants could be minimized by multi-targeting of tumor cells with pAb, which would be more efficient than mAb at mediating effector functions for target destruction. However, the use of heterologous pAb is limited by their immunogenicity. Glyco-humanization (GH) solves this issue and allows to reconsider the potential of pAb in oncology. 3 GH-pAb have already been introduced in clinic in non-oncology settings, with a good safety profile. XON7 is a new GH-pAb targeting cancer cells. Methods: Complement dependent cytotoxicity (CDC) and apoptosis against various tumor cell lines and PBMC from healthy donors were tested with XON7 at increasing concentrations (6,25 µg/mL to 400 µg/mL) Specific binding to human tumors was assessed by immunochemistry on tissue micro-array (13 sections of original tumor, 13 healthy tissues). Cross-cancer activity was evaluated on biopsies from patients with solid tumor or blood cancer: CRC (n=63), NSCLC (n=30), Osteosarcoma (n=4), pancreatic (n= 48), GIST (n=2), AML (n=10), DLBCL (n=7). Xenograft mice model: XON7 efficacy was tested in several sub cutaneous xenograft models in NMRI nude mice (n=10 per group) using A549: non-small-cell lung cancer, HCT-116: colon cancer, LnPac: prostate cancer, KMS-12-BM: myeloma, T1301: T cell lymphoma. Treatments (35mg/kg, twice a week) were given for 4 weeks once the tumor reached 50 mm 3 . Results: XON7 induced specific human tumor cell lines CDC (IC50=50ug/mL) and apoptosis (IC50= 100ug/mL) up to 100% of the cells, without cross-reactivity with healthy human cells. XON7 targets several patients’ tumoral tissues. In vivo, XON7 induces a significant reduction of tumor growth ranging from 40 to 90% across all tested tumors. Conclusions: Immunotherapy with XON7 could be a novel therapeutic approach to fight solid tumors and hematological malignancies. [Table: see text]
Efficacy and safety of darolutamide in Chinese patients with metastatic hormone-sensitive prostate cancer (mHSPC): A subpopulation analysis of the phase 3 ARASENS study.
Authors: Shanshan Wang, Cheng Fu, Qing Zou, Youyuan Li, Dalin He, Shaogang Wang, Hongkai Wang, Matthew Raymond Smith, Bertrand F. Tombal, Maha H. A. Hussain, Yi Niu, Ling Cai, Nan Hu, Shiyun Huang, Shivani Kapur, Rui Li, Iris Kuss, Dingwei Ye
Journal: Journal of Clinical Oncology (2023)

e17076 Background: Darolutamide (DARO) is an androgen receptor inhibitor approved in China for the treatment of nonmetastatic castration-resistant prostate cancer (CRPC). In the global ARASENS trial, DARO significantly increased overall survival (OS) vs placebo (PBO) in patients (pts) with mHSPC. The efficacy and safety of DARO in the Chinese subpopulation of ARASENS are reported here. Methods: In this randomized, double-blind phase 3 trial, 1305 pts with mHSPC were randomized 1:1 to receive DARO 600 mg orally twice daily or PBO, in combination with androgen-deprivation therapy (ADT) and docetaxel. The primary endpoint was OS. Results: In mainland China, 202 pts were randomized to the DARO group (n = 104) or the PBO group (n = 98). Demographics and baseline characteristics were well balanced between treatment groups and comparable to the overall ARASENS population, except for a slightly higher proportion of pts with Gleason score ≥8, higher proportion with metastatic disease at diagnosis, and higher median baseline prostate-specific antigen (PSA) in Chinese pts vs the overall population. The risk of death was reduced by 36% (HR 0.64, 95% CI 0.41–0.99) with DARO vs PBO in Chinese pts (Table). The key secondary endpoint time to CRPC (HR 0.32, 95% CI 0.20–0.50) and the exploratory endpoint time to PSA progression (HR 0.22, 95% CI 0.13–0.37) also favored DARO. In the DARO group, 81% of pts had a maximum PSA decline of ≥90% from baseline (PSA90) at week 12, while 88% had PSA90 and 71% reached PSA &lt; 0.2 ng/mL at any time. Incidences of treatment-emergent adverse events (TEAEs) in Chinese pts were similar between treatment groups and comparable to the overall population. The most common grade 3/4 TEAE in Chinese pts was neutropenia (DARO 64%, PBO 62%), a known toxicity of docetaxel; grade 3/4 febrile neutropenia occurred in 4.0% of Chinese pts compared with 7.6% in the overall population. Conclusions: In the ARASENS subpopulation of Chinese pts with mHSPC, DARO + ADT + docetaxel showed favorable efficacy and safety vs PBO + ADT + docetaxel: OS and clinically relevant secondary endpoints favored DARO vs PBO, and the incidences of TEAEs were similar in the two treatment groups. These results are consistent with the findings reported for the overall population in ARASENS. Clinical trial information: NCT02799602 . [Table: see text]
Shattering myths regarding Hispanic ethnicity and survival in acute myeloid leukemia: Insights from the National Cancer Database.
Authors: Naveen Premnath, Adeel Khan, Mohak Pandey, Urvashi Pandey, Fieke W Hoff, Stephen Chung, Praveen Ramakrishnan Geethakumari, Robert Collins, Elizabeth Paulk, John W. Sweetenham, Yazan F Madanat
Journal: Journal of Clinical Oncology (2023)

7032 Background: Previous smaller studies suggest that despite younger age at presentation, Hispanic patients (HP) with acute myeloid leukemia (AML) have worse prognosis than non-Hispanics patients (NHP). Methods: We queried the National Cancer Database (NCDB) between 2004 to 2017 for adults aged ≥18 years for a diagnosis of AML using the ICD-O-3 diagnosis code. Baseline characteristics and outcomes were compared. Results: A total of 144,146 patients with AML were identified during the study period of which 9173 were Hispanic (6.4%). The median age at diagnosis was 66 years overall. Hispanics were younger at presentation with median age 55 compared to 67 in non-Hispanics ( p&lt; 0.001). A higher proportion of HP were uninsured and in the lowest income quartile compared to NHP across all AML subtypes. HP had statistically significant longer survival across AML subtypes except for tAML. When adjusted for age, sex, Charlson Deyo Comorbidity Index, insurance, chemotherapy, transplant, and income status using a multivariate Cox regression analysis, HP had non-inferior survival to NHP. Conclusions: We present the largest study to date in Hispanics with AML. Hispanics presented at younger ages and had worse socioeconomic factors compared to NHP and when adjusted for multiple variables, did not have worse outcomes as reported in prior data. We believe previous studies in HP demonstrating worse prognosis may reflect bias and confounding given smaller patient numbers and are suggestive of disparities in access to health care and present opportunities for improvement. [Table: see text]